The objectives of this research are to identify some of the mechanisms by which histocompatibility (H-2) linked I-region genes (including immune response, Ir, genes) control the immune response to Chicken hen egg-white lysozyme (HEL) in the mouse and to determine the cellular site of their effect. The specific aims are to test the ability of I-region genes to restrict cell interactions between T cells and B cells but, more importantly, between different T-cell subsets. This will be accomplished by testing the immune function of well-defined T-cell subsets during in vivo and in vitro anti-HEL responses. Effector populations will be derived from normal (responder x nonresponder) F1 mice, (R x NR) F1, or irradiation bone marrow chimeras of the parent to (R x NR) F1 and (R x NR) F1 to parent combinations. Second, the fine specificity of HEL-primed T cells derived from chimeric and normal mice will be examined in antigen-specific T cell proliferation and T helper cell assays to assess the influence of MHC gene products on the acquisition of the T-cell repertoire specific for HEL. The identification of T-cell subsets possessing new antigenic specificities associated with a new restriction in cell interactions, will provide insight into mechanisms of I-region controled cell interactions. Third, T cells from chimeric and normal mice will be used as fusion partners in somatic cell hybridization protocols to prepare suppressor factor, interleukin-2 (IL-2), and other regulatory lymphokine-producing hybridomas. The T hybridomas and their mediators are particularly appropriate for studies designed to define the fine specificity of T-cell responses to HEL. The immunobiology of mediators that are themselves antigen-binding or produced by T hybrids after antigen stimulation will be evaluated in both anti-HEL T-cell proliferative responses and in in vitro antibody responses. Consequently, a better understanding of the nature of determinants involved in regulation of responses to antigens exhibiting MHC control will be achieved by integrating the immune function of antigen-specific T-cell hybridomas, normal T cells, and chimeric T cells. (LB)